How Opioids Affect Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine Treatment for Depression & Chronic Pain in Older Adults

Chronic low back pain and depression are common and frequently co-occurring in late life. Yet treatment can be challenging as these conditions are risk factors for each other, and both interfere with the other’s treatment response. Opioids may be a marker of poor treatment response for both depression and pain. In addition, there is limited evidence of the efficacy of opioids for patients with chronic pain, and exposure to opioids in older adults has been associated with long-term disability, increased risk of dependency, recurrence of depression, and other negative neuropsychiatric outcomes. While chronic pain seems to be associated with worse depression outcomes, it is not known if the efficacy of antidepressants for older patients living with both depression and chronic pain is negatively affected by co-prescribed opioids. While the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine is considered an effective treatment for depression and may improve chronic pain for some patients, there are few clinical trials that have investigated the clinical outcomes of co-prescribed opioids and SNRIs.

To improve understanding of pain and mood response to venlafaxine, relative to opioid exposure, among older adults with chronic low back pain and depression, a team including Sarah T. Stahl, PhD, and Jordan F. Karp, MD, conducted an analysis of 227 adults, age 65 and older, living with depression and chronic low back pain. The team hypothesized that opioid use, and increased exposure to opioids, would be associated with worse pain and depression outcomes in response to six weeks of venlafaxine treatment. “We suspected that opioids might reduce the analgesic effects of antidepressants and make venlafaxine less effective at relieving pain and depression symptoms in older adults,” explained Dr. Stahl, the study’s first author.

Using data gathered from the Addressing Depression and Pain Together randomized clinical trial, the investigators conducted an analysis of participating older adults who received six weeks of treatment in which venlafaxine was increased up to 150mg per day (or the highest tolerated dose). Of these 227 participants, 81 (36%) were co-prescribed an opioid to treat their chronic low back pain. 

The investigators found that in individuals age 65 and older with depression and chronic low back pain, being prescribed an opioid did not decrease the odds of experiencing either a depression response or a combined pain/depression outcome, but patients co-prescribed an opioid were less likely to report a pain response to treatment with venlafaxine. In addition, the higher the dose of opioids, the less likely patients were to have an improvement in their pain. 

Dr. Karp, the study’s senior author, elaborated on the findings: “For these patients, clinicians may want to consider non-opioid or alternative analgesic approaches for pain management. It is reassuring that opioids did not prevent depression response in older patients living with depression and pain. The fact that 36% of these patients with depression and chronic low back pain were prescribed opioids is troubling, given their burden of symptoms despite receiving these medications.”

Opioid Exposure Negatively Affects Antidepressant Response to Venlafaxine in Older Adults with Chronic Low Back Pain and Depression
Stahl ST, Jung C, Weiner DK, Peciña M, Karp JF.

Pain Medicine 2019 DOI: 10.1093/pm/pnz279